Fibrinogen is the precursor of fibrin, the material of which blood clots are composed. It is a large molecular weight glycoprotein composed of two pairs of three non-identical polypeptide chains. A high resolution X-ray structure of the whole molecule has yet to be obtained. Recently, we determined the structures of the principal proteolytic fragment of human fibrinogen, fragment D, and also of the corresponding fragments from factor XIII crosslinked human fibrin (double-D). We have also managed to co-crystallize both of these entities with two different synthetic peptides that correspond to the polymerization knobs found on the fragment E part of fibrinogen. All told, we have been able to obtain seven different (but closely related) structures. The resolution of the various structures ranges from 2.9 to 2.3 E. A number of conformational changes have been found that correspond to various steps in the early stages of the fibrinogen to fibrin conversion. We also have crystals of the important complex known as "D2E." Although the crystals are small, it is our hope that we will be able to collect sufficient data of a high enough quality that the fragment E portion will be apparent with a molecular replacement solution alone.